Journal of the Korean Pediatric Society 2003;46(7):702-709.
Published online July 15, 2003.
Sensitization of TNFα and Agonistic FAS/CD95 Antibody-Induced Apoptosis by INFγ on Neuroblastoma Cells
Ho Il Bang, Jong Duck Kim, Du Young Choi
Department of Pediatrics, School of Medicine, Wonkwang University, Iksan, Korea
신경모세포종에서 IFNγ에 의한 TNFα와 길항적 FAS/CD95항체 유도성 세포고사의 감작화
방호일, 김종덕, 최두영
원광대학교 의과대학 소아과학교실
Du Young Choi, Email:
: IFNγ sentitizes many tumor cells to TNFα and FASL-mediated apoptosis by enhancing the expression of TNF or FAS/CD95 receptor and modulating the activation of caspase and Bcl-2 family. It has been reported that IFNγ and TNFα synergistically caused differentiation and growth inhibition of neuroblastoma cells. Even though some neuroblastoma cell express FASR/FASL on the cell surface, they could not induce apoptosis by ligation of the FAS/CD95 receptor. But the treatment of IFNγ is reported to induce apoptosis in some neuroblastoma cell lines through the CD95/ CD95L autocrine circuit. In this study, we examined whether IFNγ could affect TNFα and agonistic FAS/CD95 antibody(CH-11)-induced apoptosis against neuroblastoma cell lines that had shown diverse drug sensitivity and resistance.
: CHLA-15, CHLA-90 and LA-N-2 neuroblastoma cells were cultured in IMDM and treated with recombinant IFNγ, TNFα and CH-11 antibody. Cell viability was measured by DIMSCAN with a fluorescent calcein-AM. Apoptosis was analyzed through flow cytometry using Annexin V- PE and 7-ADD staining and confirmed by pancaspase and caspase-8 blocking experiments. The expression of TNF RI and FAS/CD95 receptor was evaluated by flow cytometry using the corresponding antibody and PE-conjugated secondary antibody.
: IFNγ or TNFα alone had no demonstrable cytotoxic effects, whereas both cytokines in combination induced apoptosis synergistically in CHLA-15 and CHLA-90 cells. Although there was no cytotoxicity with the ligation of CH-11 alone in CHLA-90 cells, pretreatment of IFNγ increased the sensitivity of CH-11-mediated apoptosis. The expression of TNFRI and FAS/CD95R were nonspecifically enhanced after treatment of IFNγ without relation to sensitivity to TNFα and CH-11. This finding suggest up-regulation of both receptors may contribute to sensitization of TNFα and CH-11-mediated apoptosis by IFNγ in only sensitive cell lines.
: IFNγ induced sensitization of TNFα and agonistic FAS/CD95 antibody-mediated apoptosis on some neuroblastoma cells through up-regulation of TNFRI and FAS/CD95 receptor.
Key Words: Neuroblastoma, IFNγ, TNFα, Agonistic FAS/CD95 antibody(CH-11)

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